The main aim of this proposal is to seek information on the response of T lymphocytes to Mls determinants; these determinants are expressed on a subset of B cells and are strongly stimulatory for T cells. We are primarily interested in two particular questions: (1) Are the receptors used by T cells to recognize Mls determinants the same or different to the receptors for conventional antigens? We have preliminary evidence that anti-Mls receptors might indeed be different. This evidence stems from the finding that T hybridomas with dual specificity for Mls and conventional antigens can lose reactivity for one set of antigens but not the other. Using a variety of techniques, including examination of T hybridomas at the DNA level and production of T-cell-receptor-specific monoclonal antibodies, we seek direct evidence that a unique and separate set of receptors control the T-cell response to Mls determinants. (2) How do T cells "see" Mls determinants on B cells, particularly on resting small B cells. We propose to test the idea that, for B cells to present Mls determinants, the cells require prior activation. We will examine whether exposing B cells to treatments that inhibit cell activation concommitantly inhibits presentation of Mls determinants. We also will address the question of the role of Ia determinants in Mls-specific responses. (AG)